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The article is devoted to the important problem of diagnosis and treatment of children with autonomic dysfunction syndromes (SVD). Information is provided on the evolution of views on the pathogenesis of this condition. The issues of pathogenesis, classification and clinical manifestations of SVD in children and adolescents are covered in detail. The high effectiveness of the use of Mexidol in the complex correction and prevention of manifestations of SVD, as well as concomitant neuropsychiatric disorders in children and adolescents has been demonstrated.

Arterial hypertension (AH) is a leading risk factor for cardiovascular diseases including cerebrovascular complications. Strokes and/or vascular cognitive impairment (VCI) are considered as a clinical sign of brain damage as a target organ in hypertension. To identify and assess the severity of VCI, patients with hypertension should undergo a neuropsychological assessment. Neuroimaging confirm the vascular origin of cognitive impairment. Patient management should include antihypertensive therapy along with neuroprotection. Among different neuroprotective therapy, ethylmethylhydroxypyridine succinate (mexidol) is one of medication with serious evidence of clinical efficacy.

Objective: To assess the clinical efficacy and safety of Mexidol in patients in acute period of ishemic stroke in the vertebral-basilar system (iiVBS)., Material and Methods: An open randomized comparative study involved 52 patients. 32 of them received Mexidol (mail group, MG) and 20 received therapy without neuroprotective drugs. Assessment of the severity of clinical manifestations of iiVBS was performed using the Hoffenberth scale, stroke severity was assessed using the NIHSS, the modified Rankin Scale was used to assess the degree of disability in patients after stroke, neuropsychological examination of patients was performed using the Montreal Cognitive Assessment (MoCA), dynamics were compared on the Hospital Anxiety and Depression Scale (HADS), Subjective assessment scale for asthenia (MFI-20), the patients' quality of life was assessed using the EQ-5D., Results: The use of Mexidol in the form of long-term sequential therapy in the patients of the MG led to a 53.3% decrease in the severity of clinical manifestations of iiVBS and a 59.5% decrease in neurological deficit according to the NIHSS scale. By the end of Mexidol therapy, 96.9% of patients MG were able to manage their own affairs without assistance (modified Rankin Scale), which was accompanied by regression of emotional disturbances and improved quality of life of patients., Conclusion: Administration of Mexidol in therapy of patients with acute iiVBS can be considered the most justified, since it contributes to an earlier and more significant reduction of neurological deficit and improvement of patients' quality of life.

Objective: To conduct a meta-analysis of the effectiveness of Mexidol therapy in patients with chronic brain ischemia (CBI) and cognitive disorders (CD)., Material and Methods: This meta-analysis included the results of studies on the effectiveness of Mexidol in patients with CD measured with Montreal Cognitive Assessment Scale (MoCA). The pooled effect assessment included all publications from independent clinical trials that provided efficacy data on the MoCA scale with a level of detail sufficient for further mathematical analysis. The main result of the meta-analysis was obtained for the final values of the effectiveness indicator in the Mexidol groups compared with the basic therapy groups. Data from 10 prospective randomized trials containing information on the final scores on the MoCA scale after therapy was analyzed., Results: The meta-analysis of ten prospective clinical studies of the effectiveness of Mexidol against the background of basic therapy in patients with CCI and CD was carried out. The total number of patients taking Mexidol was 482; the comparison group consisted of 455 patients. According to the results of a statistical model of random effects, the effect size was 2.06; 95% confidence interval for the difference in effectiveness between the groups of the study drug and the control groups [0.98; 3.14] ( p =0.0002)., Conclusion: A statistically significant and clinically significant improvement in the cognitive functions of patients with CBI, was demonstrated after treatment with Mexidol.

Stroke is an acute life-threatening condition; its outcome is determined by the degree of damage to brain tissue, the quality and speed of medical care in the first minutes and hours after its occurrence. The main mechanism of brain tissue damage during both ischemia and reperfusion is oxidative stress. The review covers adverse influence oxidative stress at the cerebral ischemia and reperfusion periodes of ischemic stroke. The results of preclinical studies demonstrating the ability of Mexidol to neutralize the effects of free radicals and activate antioxidant protection are presented. Data from clinical studies of the use of Mexidol in combination with thrombolysis in patients with ischemic stroke are reviewed.

Objective: Evaluation of the effect of pharmacological modulation of the rehabilitation process with the drug mexidol as an adjuvant component of the rehabilitation treatment of cognitive-emotional disorders in patients who have suffered acute cerebral insufficiency (ACI) due to acute cerebrovascular accident or traumatic brain injury., Material and Methods: The study was conducted as a randomized interventional prospective study and consisted of 5 visits. Patients were divided into 2 groups: main ( n =30, standard therapy + Mexidol IV 500 mg per day for 10 days, followed by Mexidol FORTE 250 orally, 1 tablet 3 times a day for 8 weeks) and control ( n =30, standard therapy for 66 days)., Results: The study randomized 60 patients who underwent ACN and received rehabilitation treatment in accordance with regional routing. In the main group, there was an improvement in cognitive functions comparable to the control group ( p <0.001, in both groups there was an improvement in the Schulte test «work efficiency» and «total execution time», according to the MoCA scale (visit 5 - 23.8±2.6 vs 22.9±31, p =0.227). A significant superiority of the main group over the control group was shown in such indicators as a decrease in anxiety (according to the HADS scale) (visit 4 - 2.6±2.4 vs 4.4±2.4, p =0.004), a decrease in the severity of depression (according to the Beck scale) (visit 3 - 7.5±4.5 vs 11.4±5.6, p =0.005). There was a tendency for the main group to be superior in terms of muscle strength (according to the MRC scale (visit 4 - 3.3±5.1 vs 2.1±2.2, p =0.051), level of vital activity (according to the ShRM - visit 5 - 2.9±0.7 vs 3.3±0.6, p =0.053). A statistically significant increase in the level of mobility of patients in the group using the drug Mexidol was proven compared to the control group (the difference in the Rivermead index at the 5th visit was 10.3±2.8 and 8.0±2.8, respectively, p =0.006), the average increase in the Rivermead index by visit 5 (5.4±2.1 vs 3.4±1.6, p <0.001). A decrease in intensive care aftereffects syndrome (ITS) scores was detected in both groups; a statistically significant decrease in the severity of ITS in relation to the previous visit was detected only in the group using the drug Mexidol ( p <0.001). In the main group, the best indicators of the dynamics of systolic cerebral blood flow velocity and overshoot coefficient were also determined, compared to the control group. There were no adverse events recorded in the study., Conclusion: A positive modulating effect of Mexidol has been demonstrated in terms of accelerating the restoration of tolerance to cognitive loads, improving the psycho-emotional background by reducing symptoms of anxiety and depression, and secondary improving the results of motor rehabilitation in the early recovery period in patients who have undergone ACI, including those with manifestations of PIT syndrome. During the study, no adverse events were recorded, as well as significant differences in vital functions in the study groups, which indicates comparable safety of therapy in the control and main groups.

The review is devoted to a comparative analysis of the clinical efficacy of the original domestic derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) in comparison with the results of an experimental study of their dopaminergic action. The position that the dopaminomimetic activity of emoxipin, reamberin and mexidol largely determines their anti-ischemic, antihypoxic, insulin-potentiating neuroprotective, nootropic and antidepressant potential has been substantiated. A comparative analysis of the safety profile of emoxipine, reamberin and mexidol was carried out, taking into account potential and real side-effects caused by iatrogenic deviations from the eudopaminergic state. It has been shown that mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which is simultaneously a derivative of 3-hydroxypyridine and succinic acid, has the best balance of efficacy and safety. A generalized assessment of the available data on the successful use of off-label derivatives of 3-hydroxypyridine and succinic acid indicates the advisability of a significant expansion of indications for their clinical use. The authors resume that the «therapeutic retargeting» of emoxipin, reamberin and mexidol (i.e. their use for qualitatively new indications) will contribute to progress in the treatment of socially significant and most common diseases.

Objective: To evaluate systematically the published peer-reviewed literature and estimate the effect of therapy with Mexidol on the course and outcomes of ischemic stroke (II) in adult patients., Material and Methods: The meta-analysis included 11 studies reported In Russian (2 randomized controlled studies, 9 non-randomized, unblinded cohort studies)., Results: The results obtained indicate a positive effect of Mexidol on the course of II in the treated adult patients: we found statistically significant decrease in NIHSS scores on days 7-10 and 21-24 and in modified Rankin scale scores on days 5-7 and days 10-14 compared with the control group. The cumulative effect of the drug was shown: the between-group difference of the NIHSS scores increases with the course of observation time. The effect of Mexidol on indicators on the NIHSS scale is more significant, the greater the initial severity of the patient's neurological deficit., Conclusion: Heterogeneity in study designs and patient characteristics has resulted in significant statistical heterogeneity, and the evidence presented at the time of writing requires further examination as new data become available.

Mexidol (ethylmethylhydroxypyridine succinate) is a modern neurometabolic medication increasingly being used in neuropediatrics. The results of recent studies confirming the positive effects of Mexidol pharmacotherapy in children with attention deficit hyperactivity disorder (ADHD), perinatal damages of the central nervous system (hypoxic-ischemic encephalopathy) and their consequences, neurological disorders and neurodevelopmental delay after surgery for congenital heart defects, neuroinfections (meningitis, encephalitis), posttraumatic epilepsy. Taking into account the unique multimodal action of Mexidol, it seems promising to expand the range of indications for its application in neuropediatrics, based on the results of new clinical trials organized in accordance with modern principles of evidence-based medicine.

The problem of postcovid syndrome (PCS) attracts great interest due to the wide prevalence and variety of clinical manifestations. The main neurological manifestations of PCS are considered. The information about the proposed mechanisms of the formation of PCS is given. The possibility of using the drug Mexidol for the treatment of patients with PCS is discussed.

Research Aim: To study the RBCs functional and metabolic parameters and the microcirculatory brain structure at traumatic brain injury (TBI) under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate., Methods: A closed TBI was modeled by the free fall of a load on the parietooccipital regions of head. We made studies of the influence of 2-ethil-6-methil-3-hydroxipiridin succinate on aggregation and electrophoretic mobility of RBCs, catalase activity, malonic dialdehyde concentration, adenosine triphosphate and 2.3-biphosphoglycerate (2.3 - BPG) concentrations in RBCs. The state of parenchyma and microcirculatory brain mainstream in post-traumatic period of TBI have been studied on micro-preparations., Results: The use of 2-ethyl-6-methyl-3-hydroxypyridine succinate under conditions of head injury leads to a decrease in MDA concentration and in aggregation of RBCs, to an increase in the 2.3-BPG concentration and RBC electrophoretic mobility compared to the control (group value). The most pronounced changes under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate were observed 3-7 days after the TBI. Significant indicators of the restoration of the microvasculature and brain tissue provoked by the use of 2-ethyl-6-methyl-3-hydroxypyridine succinate of were evident from the 7th day unlike the control group, where the restoration of structural morphological parameters was observed only on the 12th day of the post-traumatic period. Fast recovery of blood flow under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate ensured effective restoration of neurons and glia in comparison with the control group., Conclusions: Early and long-term cytoprotective correction intensifies the oxygen transport function of the blood, prevents and / or reduces disorders of microvessels, neurons and glia in the post-traumatic period, thereby provides correction of hypoxic state and drives to the restoration of brain tissues homeostasis., (© 2021. The Author(s).)

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clinically relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4 . Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clinical stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC).

Objective: To study the possibility of improving the efficacy of treatment with mexidol in COVID-19 patients with chronic cerebral ischemia (CCI)., Material and Methods: Three hundred and four patients with CCI and COVID-19 were observed, group 1 ( n =152) consisted of patients receiving basic therapy and mexidol, group 2 ( n =152) received only basic therapy. Mexidol was administered intravenously for 14 days, 500 mg (10 ml) per 400 ml of saline solution, then Mexidol FORTE 250 was administered in a dose of 250 mg 3 times a day for 2 months. The state of cognitive functions (MoCA scale), sleep (Spiegel questionnaire), asthenia (MFI-20 scale), and quality of life (SIP questionnaire) were evaluated. Examinations were performed before treatment, 30 and 75 days after start of treatment., Results: In group 1, there was a more complete and earlier recovery of the state of cognitive functions (an increase in indicators on the MoCA scale, p <0.01), a regression of asthenia ( p <0.05), and normalization of sleep ( p <0.01). By the end of the study, there were significantly more patients in group 1 with complete or significant recovery of all quality of life indicators., Conclusion: Long-term sequential therapy with mexidol provides a more complete recovery of impaired functions in patients with CCI and COVID-19.

Aim: To study the efficacy and safety of mexidol's intravenous injections (500 mg once a day) for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic cerebral ischemia (CCI) in patients with hypertension and atherosclerosis of the brachiocephalic arteries., Material and Methods: The observation program included 60 patients with an established diagnosis of CCI confirmed by neuroimaging methods. Patients of the main group (n=26) received mexidol along with basic therapy, patients of the comparison group (n=26) received only basic therapy., Results and Conclusion: The results of the experience show the high efficacy and safety of sequential therapy (parenteral therapy followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases static-motor disorders and severity of subjective neurological symptoms. High adherence of patients to the therapy is shown.

Aim: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification., Material and Methods: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed., Results: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo ( p <0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years ( p =0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms ( p =0.049 and p =0.02) and an increase in patients without problems with everyday activities ( p =0.007 and p =0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity ( p =0.023) and quality of life ( p =0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups., Conclusion: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.

Aim: To evaluate an effect of long-term sequential therapy with mexidol and mexidol forte on the functional outcome of patients with carotid ischemic stroke., Material and Methods: The study included 50 patients with newly developed carotid stroke, hospitalized in the stroke unit on the first day from the onset of the disease. Patients of the main group (n=25) received mexidol in a dose of 500 mg intravenously once a day for 14 days, then mexidol forte 250 in tabs 250 mg 3 times a day for 60 days. Patients of the comparison group (n=25) received standard basic therapy. The significance of intergroup differences was assessed using the Mann-Whitney test, Fisher's exact test, and relative risk (OR) calculation. Differences were considered significant at a level of p<0,05., Results: After 14 days of therapy, both groups of patients showed a positive trend compared to baseline. At the same time, patients of the mexidol group had a higher MoCA score (U=173,5, p=0,006), a lower score when performing tasks on dynamic praxis (U=214,0, p=0,028) and optical spatial disturbances (U=170,5, p=0,003), better memorization strength (181,5, p = 0,006) and better performance on abstraction MOCA subtest (U=200,5, p=0,014). By the 74th day, the absence of moderate cognitive impairment (MoCA> 26 points) was diagnosed in 17 patients (68%) of the main group and 14 patients (56%) of the comparison group. No significant differences were found. Moreover, patients of the main group had a significantly lower NIHSS score (U=124,0, p<0,001) and a lower degree of disability: a total mRS score 0-2 was achieved in 19 (76%) patients of the main group and only in 12 (48%) patients of the comparison group (OR=3,34, F=0,07, p<0,05). Also, patients receiving long-term sequential therapy with mexidol and mexidol forte 250 had milder spatial disorders than patients of the comparison group., Conclusion: Consecutive treatment with mexidol and mexidol forte 250 in the acute and early recovery periods of ischemic stroke positively affects the regression of local neurological symptoms, increases the likelihood of achieving independence in everyday life by 3,34 times, and reduces the severity of optical-spatial, neurodynamic and memory impairments.

We report that compound 13 , a novel phosphatidylserine-targeting zinc(II) dipicolylamine drug conjugate, readily triggers a positive feedback therapeutic loop through the in situ generation of phosphatidylserine in the tumor microenvironment. Linker modifications, pharmacokinetics profiling, in vivo antitumor studies, and micro-Western array of treated-tumor tissues were employed to show that this class of conjugates induced regeneration of apoptotic signals, which facilitated subsequent recruitment of the circulating conjugates through the zinc(II) dipicolylamine-phosphatidylserine association and resulted in compounding antitumor efficacy. Compared to the marketed compound 17 , compound 13 not only induced regressions in colorectal and pancreatic tumor models, it also exhibited at least 5-fold enhancement in antitumor efficacy with only 40% of the drug employed during treatment, culminating in a >12.5-fold increase in therapeutic potential. Our study discloses a chemically distinct apoptosis-targeting theranostic, with built-in complementary functional moieties between the targeting module and the drug mechanism to expand the arsenal of antitumor therapy.

Background: Colonoscopy remains the gold standard for the investigation of abnormalities within the colon. However, its success is highly dependent on the quality of bowel preparation. The objective of this study was to compare the bowel preparation efficacy of picosulfate/magnesium citrate (PMC) vs polyethylene glycol (PEG) in a one-day vs two-day split dose regimen., Methods: A prospective, randomized, controlled trial was conducted at the Forzani & MacPhail Colon Cancer Screening Centre in Calgary, Canada. 171 colonoscopy outpatients were randomized to split-dose PMC or PEG lavage as well as into one-day split or two-day split regimens in blocks of eight. Bowel preparation quality was recorded in a blinded manner by the endoscopist using the Ottawa Bowel Preparation Scale (OBPS) prior to washing or suctioning. The scale results were analyzed using a two-factor analysis of variance., Results: 141 patients received complete colonoscopies (PMC-71; PEG-70). PEG was found to be superior to PMC (mean OBPS: 4.14 ± 2.64 vs 5.11 ± 3.44, p = 0.019), when adjusted for administration regimen, leading to significantly more adequate bowel preparations (79.7% vs 59.7%, p = 0.007). A two-day split dose was superior to a one-day split dose regimen (mean OBPS: 3.68± 2.82 vs 5.69 ± 3.06, p<0.001). Two-day split dosing also resulted in a better right colon cleanliness score (right bowel OBPS 1.27±0.11 vs 2.10±0.12 for one-day split, P<0.001)., Conclusions: Optimal bowel preparation was achieved with the use of PEG lavage when administered in a two-day split dose regimen. This trial is registered with ClinicalTrials.gov under identifier NCT01415687., Competing Interests: The authors have declared that no competing interests exist.

Aim: To study the efficacy and safety of Mexidol used intravenously (500 mg 1 time per day) for 14 days, followed by the oral administration of Mexidol Forte 250 in a dose of 250 mg 3 times a day for 60 days, in patients with chronic cerebral ischemia (CCI)., Material and Methods: The study included 56 patients with CCI due to a combination of hypertension and atherosclerosis. The results of physical examinations (control of blood pressure, heart rate etc.), dynamics of complaints, scores on CGI, MoCa, MFI-20, HRSD, HARS and the Tinetti test were evaluated., Results and Conclusion: The high level of efficacy and safety of intravenous injections of Mexidol followed by the oral administration of Mexidol Forte 250 are demonstrated. This scheme of therapy contributes to a significant decrease in the objective and subjective symptoms of CCI, leads to improvements in the emotional, cognitive and motor spheres.

Aim: To study the efficacy and safety of mexidol dripped intravenously (500 mg once a day) in the form of infusions for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic brain ischemia in patients with hypertension and atherosclerosis., Material and Methods: The open observation program included 60 patients with an established diagnosis of chronic brain ischemia confirmed by neuroimaging methods., Results and Conclusion: The results of the study show the high efficacy and safety of sequential therapy (injections followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases motor disorders and severity of subjective manifestations. High adherence of patients to the therapy is shown.

Objectives: Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC). Stimulant laxatives are associated with harmful long-term colonic effects and possible carcinogenic risk - and evidence support that these agents are used for longer periods. We aimed to compile and review the clinical trial evidence describing the effectiveness and safety of long-term treatment (>14 continuous days) with stimulant laxatives., Methods: The PubMed database was searched for all randomised clinical trials (RCTs) examining the effect of bisacodyl or sodium picosulfate in adult patients diagnosed with constipation., Results: Five RCTs (one open-label and four double-blinded) with intervention periods of four weeks duration were eligible. These included 1008 patients, whereof 26% dropped out. A positive global assessment of efficacy was obtained in 78-99% of the patients treated with bisacodyl or sodium picosulfate. Notably, the same global assessment was obtained in 46-54% of the placebo-treated patients. Compared to placebo, an improvement in stool consistency and a significant increase in number of bowel movements peer week were seen in favor of bisacodyl and sodium picosulfate. However, for pyridostigmine, a significant difference was seen compared to bisacodyl. AEs were generally mild, but frequent (up to 72%) mostly diarrhea and abdominal pain., Conclusion: The evidence base does not support use of stimulant laxatives for more than four weeks. Due to the substantial use of stimulant laxatives including sold OTC, longer term RCTs and epidemiological studies investigating effects and safety on the longer term are warranted.

This review summarizes the available data on the combined administration of mexidol with medicines of different pharmacotherapeutic groups. Mexidol has a multifaceted mechanism of action and exhibits a wide range of pharmacological effects. It enhances therapeutic effects of a variety of drugs in research and clinical settings, boosts the effectiveness of therapy prescribed in accordance with the applicable federal standards and contributes to reducing the severity of complications. Effectiveness data and pathogenetic considerations underpinning combination therapy with mexidol and other drugs suggest that this is a viable approach for treating cerebrovascular and cardiovascular diseases, diseases of the nervous system, open-angle glaucoma and alcohol intoxication as well as a number of other diseases.

To study rheological properties of blood in patients with acute ischemic stroke treated with mexidol., Material and Methods: Sixty patients with acute stroke, including 32 patients who received mexidol (500 mg/IV/20 days) and 28 people who received magnesium sulfate (2000 mg/IV/20 days) were examined. The control group included 20 people without a cardiovascular pathology. Blood rheology (viscosity of whole blood, plasma viscosity, hematocrit, aggregation and deformability of erythrocytes, fibrinogen level) was evaluated in patients three times: for the first 12 hours, 3-5 days and 18-20 days after hospitalization., Results: Hyperviscosity syndrome was observed in all patients with stroke. A significant decrease in blood viscosity was found in patients treated with mexidol: in the 3-5th day at low shear rates and in the 18-20th day at 3-100 s -1 shear rates. Significant differences in hematocrit (p=0.026) and fibrinogen levels (p=0.017) in patients treated with different drugs were found in the 18-20th day of the disease. Higher erythrocyte deformability index was recorded in patients treated with mexidol in the 3-5th day at shear rates of 90 and 890 s -1 , in the 18-20th day at shear rates of 90-360 s -1 ., Conclusion: The study confirms the impact of mexidol on the fluidity of blood during the acute cerebral ischemia and shows its efficacy in reducing blood viscosity, decreasing the level of hematocrit and fibrinogen, increasing the deformability of erythrocytes.

Sensorineural hearing loss can develop as a consequence of vascular pathology. The etiology and pathogenesis of chronic sensorineural hearing loss allow us to consider promising the use of neuroprotective drugs in the treatment regimen that can activate the function of the neural structures of the auditory pathway. Ethylmethylhydroxypyridine succinate, having complex pharmacological capabilities and a wide range of effects realized at the neural and vascular levels can be used in the treatment of hearing impairment and speech intelligibility.

Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the "price" of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions These results indicate that increasing the "price" of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To obtain optimal visualization of the colonic mucosa during gastrointestinal endoscopic procedures, an adequate bowel preparation is mandatory, but a standardized protocol is still lacking for pediatric patients. Polyethylene glycol (PEG) is currently the most used laxative, but the amount of liquid to be taken orally is a large volume for the pediatric population and it may not be well tolerated. The aim of our preliminary trial was to evaluate efficacy, tolerability, and safety of sodium picosulphate-magnesium citrate (SPMC) used as bowel preparation before colonoscopy in children. Fifty children who needed a colonoscopy were prospectively enrolled between April and December 2013 and SPMC was administered to them as bowel preparation. A questionnaire about the product tolerance was completed by the patients' parents. The grade of bowel preparation and any related side effect were evaluated. The mean value of the Boston Bowel Preparation Scale was 7, out of a maximum of 9. Only 5 patients had an inadequate bowel preparation. Seventy percent of the patients considered the taste of the preparation very palatable. The remaining 26% considered it not palatable or not palatable at all. During the preparation, 18% of children complained of nausea, 20% abdominal pain, 2% vomiting, and 2% manifested headache. Bowel preparation with SPMC offers an efficient alternative to PEG and allows, on equal terms of efficacy, tolerability and safety, a much lower amount of laxative to ingest, and remarkable quality, especially in infants and toddlers.

To study the efficacy of mexidol in the combination with hyperbaric oxygenation (HBO) in comparison with the standard HBO sessions in patients with acute ischemic stroke. One hundred and twelve patients were examined. In the main group, 48 patients underwent HBO and received treatment with mexidol. The control group consisted of 64 people who underwent the standard HBO sessions only. The use of combination therapy (HBO+mexidol) leads to the significantly more rapid normalization of acute phase indices which are correlated with neurological deficit reduction.

Aim: To assess the changes in the composition of plasma phospholipids in patients with chronic cerebrovascular disease treated with neuroprotectors 2-ethyl-6-methyl-3-hydroxypyridine succinate (neurox) and citicoline (neipilept), the natural metabolites involved in biochemical processes in the body, and their composition., Material and Methods: The study included 40 patients, 18 men and 22 women, aged from 54 to 72 years, with chronic cerebrovascular disease at the decompensation stage complicated with the hypertensive crisis and/or arrhythmia., Results and Conclusion: During extraction of phospholipids from blood cells, a significant decrease in the amount of total lipids was found to the end of treatment of patients who received neurox or neipilept or their combination. The study of quantitative composition of phospholipids showed no significant changes in patients treated with neurox, while the use of citicoline or combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate resulted in the increase of their total mass. There were no significant changes in the qualitative composition of phospholipid classes in blood plasma in patients treated with neurox. In patients treated with neipilept or with the combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma phosphatidylcholine was significantly increased. No significant changes in the content of phosphatidylinositol, phosphatidylserine and sphingomyelin were observed.

Aim: To evaluate the clinical efficacy, metabolic and membrane protective effects of mexidol for transient ischemic attacks (TIA) in the vertebrobasilar system in elderly patients with chronic cerebral ischemia (CCI)., Material and Methods: Fifty-three patients, aged from 60 to 74 years, with the first episode of TIA in the vertebrobasilar system and CCI were examined. Patients of the main group (n=33) received mexidol in the dose of 500 mg for 10 days along with standard therapy, patients of the comparison group (n=20) received only standard therapy. The clinical implications of TIA, laboratory indices of the state of oxidant and antioxidant systems and percentage absorption of lipid-phospholipid complexes in the infrared spectrum of blood serum were studied. The control group consisted of 20 healthy people., Results and Conclusion: The use of mexidol was associated with more rapid regression of the focal neurological deficit. Mexidol significantly reduced the intensity of lipid peroxidation and had a positive impact on the level of neuronal membrane phospholipids. Metabolic and membrane protective effects of mexidol and it's positive impact on the regression of focal neurological deficit justify its inclusion into complex therapy of TIA in the vertebrobasilar system developed in patients with CCI, especially in elderly patients.

Aim: To assess the efficacy and tolerability of mexidol used to improve cognitive impairment in patients with hypertension and clinical manifestations of chronic cerebral circulatory insufficiency., Material and Methods: Forty-two patients with chronic cerebral circulatory insufficiency and cognitive impairment were examined. MMSE, МоСА and the clock drawing test were used to assess neuropsychological status. The Morisky-Green test was administered to evaluate medication adherence. Patients were stratified into two groups: patients of the first group (n=21) received standard treatment. Patients of the second group (n=21) received additionally mexidol in dose 200 mg (4 ml) in 100 ml of NaCl isotonic solution intravenously during 10 days and then in tablets (2 tablets 0,125 mg) twice a day during 8 weeks., Results: According to the 4-item Morisky Medication Adherence Scale (MMAS), 31% of respondents were not adherent to the treatment (MMAS score 0-2), 35.7% (n=15) of patients showed high adherence (MMAS score 4), 33.3% (n=14) demonstrated low adherence (MMAS score 3). The average score on the questionnaire was 2.85. In patients treated with mexidol, the absence of complaints increased by 3 times and headache regression increased by 90%. The improvement of memory, concentration and anxiety was observed in 50%, 55%, 67% of patients, respectively. Patients treated with mexidol demonstrated more significant changes during the clock drawing test. The average change in the scores increased by 0.95 compared to the control group, where the changes were 0.54 (p<0.02). The positive dynamics on MMSE and МоСА was shown in the mexidol group that indicated the positive effect of this drug on cognitive symptoms., Conclusion: The positive impact on cognitive symptoms and health in patients with chronic cerebral circulatory insufficiency allows to recommend mexidol as add-on to standard treatment of the main disease.

Antihypoxic, antioxidant and nootropic effects of mexidol contribute to the improvement of patients with cerebrovascular pathology. The results of clinical studies show that the sequential scheme of using mexidol (first i.v. or i.m., then per os) is effective in the complex therapy of ischemic diseases of the brain, vascular surgery, therapy and rehabilitation of patients with degenerative-dystrophic changes of the spine, treatment of neurodegenerative pathology (including multiple sclerosis, Parkinson's disease and diabetic polyneuropathy), infectious neuropathies (ARVI, herpes, tick-borne encephalitis), neuropsychological and autonomic disorders.

Aim: To evaluate an effect of mono- and combined therapy with mexidol in young patients with cerebral angiodystonia., Material and Methods: Ninety patients (38 men and 52 women, aged from 25 to 44 years) with autonomic dysfunction syndrome in the form of asthenoautonomic and cephalgic syndromes treated with mexidol (group 1, 30 patients), vinpocetine (group 2, 30 patients) and with the combination of these drugs (group 3, 30 patients) were included in the study. Cerebral hemodynamics was assessed using the algorithm of complex ultrasound study, autonomic regulation with the analysis of heart rate variability, functional microcirculation with laser Doppler flowmetry before and 10 days after treatment., Results and Conclusion: Mexidol used both in mono- and combination therapies exerted autonomic stabilizing and cerebral protective effects in the treatment of cerebral angiodystonia. The improvement of cerebral hemodynamics and microhemocirculation was shown. When used in combination, mexidol and vinpocetine had the synergistic effect, moreover, the adaptation of cerebral circulation increased more rapidly compared to vinpocetine treatment. Therefore, the combined therapy (mexidol and vinpocetine) in patients with cerebrovascular pathology minimizes the likelihood of poor outcomes and can prevent the development of acute cerebral circulation disorder.

Aim: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS)., Material and Methods: A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients' participation in trial ranged from 67 to 71 days., Results: By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups., Conclusion: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.

Nowadays, there are two complementary approaches to treatment of patients with ischemic stroke: reperfusion and neuroprotection. The main purpose of neuroprotection is to intervene ischemic cascade at every stage of the pathological process and thus avoid the death of nerve cells and expand the therapeutic window for reperfusion therapy. The use of drugs with neurotrophic, antioxidant and neuroregenerative effects is pathogenically explained at all stages of post stroke rehabilitation. Ethylmethylhydroxypyridine succinate (mexidol) is a derivative of succinic acid with antihypoxic, membrane protective, nootropic, anticonvulsant and sedative action. The majority of researchers confirmed the positive effect of mexidol expressed as the marked regression of neurological deficit and wider opportunities for further early rehabilitation. The results of the randomized double blind multicenter placebo-controlled, parallel-group trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA) were published in 2017. The results of the study showed the best positive dynamics of neurological function recovery in case of timely treatment with mexidol with the following two month therapy. The safety of the long-term use of mexidol was confirmed.

Aim: To study the structure of anxiety symptom complex in patients of older age groups with amnestic, disregulatory and polymodal types of mild cognitive impairment (MCI) and determine the clinical efficacy of 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol)., Material and Methods: Thirty-two patients over 55 years of age with MCI (ICD-10 item F 06.7) seeking medical help due to anxiety were included in the study. Inclusion criteria were the compensation of concomitant diseases, absence of relevant stressful events during the last year, absence of depression. Clinical-psychopathological method and psychometric scales (HAM-A, GDS, MMSE, CGI-S, CGI-I) and a stressful life events list were used. Reduction of the total score on the HАМ-А was the main criterion of the efficacy of 4-week treatment with mexidol (375 mg daily)., Results and Conclusion: At baseline, mean scores on the HAM-A and MMSE were 39,9+3.18 and 25.7+0.6 respectively. The study of the anxiety structure in patients with amnestic, disregulatory and polymodal types of MCI revealed the different phenomenology of anxiety symptom complex. Repeated assessment of anxiety on the HAM-A was performed on 1, 2 and 4 week of treatment with mexidol. The improvement of mental state was noted in all types of MCI but the better results were obtained in disregulatory and polymodal types. The rate of anti-anxiety effect was higher in the disregulatory type of MCI. In all patients, mexidol improved attention stability and autonomic function.

Developing brain ischemia due to cerebral vascularization leads to disruption of brain metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of some types of dementia. Early use of antioxidants such as ethyl ether apovincamine acid (vinpocetine) and 2-ethyl-6-methyl-3-hydroxypyridine-succinate in the treatment of this pathology is seen as a real pathogenetically based method of correction of cerebral metabolism with cerebral vascular disorders, demonstrating the increase in cerebral blood flow and also neuroprotective effects. Clinical studies and studies on biological models show that the main mechanisms of action of vinpocetine and 2-ethyl-6-methyl-3-hydroxypyridine-succinate, although have a similar focus, but implementing neuroprotective and nootropic effects via various links in the pathogenesis of ischemic brain damage.

The aim of the research - to study the Mexidol (ethylmethylhydroxypyridine succinate) effect on the factor induced by hypoxia (HIF-1α) expression in the frontal cortex of the brain in its ischemia., Material and Methods: The work was performed on the 64 male Wistar rats. The expression of HIF-1α was determined immunohistochemically., Results and Discussion: It is determined that single intraperitoneal administration of Mexidol at a dose 120 mg/kg and oral administration at a dose 100 mg/kg three times a day for 14 days is not affected the expression of HIF-1α. Unilateral occlusion of the common carotid artery increases the expression of HIF-1α at 4 hours after the occlusion. Oral administration of Mexidol at a dose 100 mg/kg three times a day for 14 days before and after ischemia increases the expression of HIF-1α after 4 and 12 hours in comparison with the norm, on the 5th day in comparison with occlusion control. Thus, it has been established that Mexidol increases the expression of HIF-1α in the frontal cortex of rat brain not under normal conditions, but in unilateral occlusion of the common carotid artery.

Aim: To evaluate the dynamics of functional activity of brain structures underlying cognitive functions in patients with encephalopathy due to poisoning with neurotoxicants on the stage of rehabilitation., Material and Methods: Fifty-six patients were examined. The main group consisted of 40 patients treated with intravenous injections with mexidol (n=10), combination of mexidol with non-pharmacological methods - mesodiencephalic modulation (MDM) (n=10), hyperbaric oxygenation (HBO) (n=10) and the combination of MDM and HBO (n=10). The comparison group included 16 people. All patients underwent neurophysiological (EEG, auditory event-related potentials) and neuropsychological examinations., Results: Marked EEG changes were noted in all patients. The domination of disturbances of functional activity on the diencephalic or mesodiencephalic levels was observed. After treatment, positive changes were found in 60% of patients. The positive dynamics was observed in 80% patients when the combination of mexidol, MDM and HBO was used. The negative dynamics was noted in 5 (12,5%) of patients of the main group, in particular when mexidol only was used. The results of the primary neuropsychological study revealed that cognitive impairment of different severity was found in 97,5% of patients of the main group and 100% of patients of the comparison group. After treatment, performance on neuropsychological tests improved by 62,5%, N200 and P300 latencies reduced, while the amplitudes increased, in the patients of the main group., Conclusion: The use of mexidol, MDM and HBO in the treatment of patients with encephalopathy due to poisoning with neurotoxicants on the stage of rehabilitation improved the indicators of functional brain activity and cognitive functions.

Aim: To perform a comparative study of anxiolytic and antidepressant effects of derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) in experimental diabetes mellitus., Material and Methods: An effect of emoxipine, reamberin and mexidol on manifestations of anxiety in 'elevated plus maze' (EPM) and duration of 'desperate behavior' (DB) in Porsolt test in rats with alloxan diabetes during medication course was studied. Alpha-lipoic (thioctic) acid (α-LA) was used as a reference drug. In additional experimental series, an effect of emoxipine, reamberin, mexidol and α-LA on the intensity of hyperglycemia in experimental DM was investigated., Results and Conclusion: All studied medications used in doses equivalent to therapeutic range in humans and administered for 14 days significantly reduced manifestations of anxiety and depression in rats with alloxan diabetes. The most pronounced anxiolytic potential was demonstrated for emoxipine that emerged as the only medication in the study that reduced manifestations of anxiety not only in comparison with 'alloxan diabetes-control' groups but also in comparison to 'intact control'. The intensity of tranquilizing activity of derivatives of 3-oxypyridine and succinic acid was similar to that of α-LA while the thymoanaleptic activity, when the drugs were administered in maximal doses to rats with experimental DM, was higher. Both emoxipine and mexidol as well as α-LA in all studied doses significantly decreased hyperglycemia in alloxan diabetes. Reamberin demonstrated only insignificant tendencies of the same trend.

Introduction: A same-day low-volume 1 L polyethylene glycol (PEG) for bowel preparation before colonoscopy was developed to improve patients' compliance. We aimed to evaluate the efficacy and safety of this regimen especially for the elderly and patients with renal dysfunction., Methods: All consecutive patients who underwent colonoscopy in our center from November 2014 to September 2015 were included. Patients undertook a low-residue diet with 10 mL sodium picosulfate 1 day before colonoscopy. Subsequently, they had 1 L low-volume PEG (MoviPrep) and 0.5 L water 4 h before the examination. Clinical outcomes, including cleansing level using the Boston bowel preparation score (BBPS), in the elderly and special-elderly (65-79 and ≥80 years old) were analyzed and compared with the non-elderly (18-64 years old). Additionally, patients with renal dysfunction were analyzed with respect to both complications and changes in blood parameters., Results: A total of 5427 patients (mean age: 64.5 ± 13.8) were analyzed. The rate of BBPS ≥ 6 in the elderly (2761 patients), special-elderly (565 patients), and non-elderly (2101 patients) was 94.1, 91.8, and 94.6 %, respectively. In the special-elderly, the rate of renal dysfunction was 14.8 %, and no severe complications were detected after colonoscopy. Additionally, there were no severe complications in 86 patients with renal dysfunction, though elevation of hematocrit was shown after intake of 1 L PEG (before, 36.7 ± 6.1 vs. after, 39.0 ± 5.7, P = 0.006)., Conclusions: Our study shows the safety and efficacy of same-day low-volume 1 L PEG bowel preparation in colonoscopy for the elderly and patients with renal dysfunction.

Introduction: Adequate bowel preparation is necessary for a complete colonoscopy. Polyethylene glycol-electrolyte oral solution (PEG-EOS), sodium picosulphate (SS) and sodium biphosphonate (SP) are the three most commonly used purgative agents. We aimed to determine their efficacy and tolerability compared to each other in a randomised study., Methods: 313 patients were randomly assigned to receive either PEG-EOS, SS or SP. Patients completed a tolerability score pre-colonoscopy. A cleanliness score was used to document adequacy of bowel preparation. A separate group of patients completed taste scores for the three cathartic agents before and after addition of flavour., Results: PEG-EOS was the worst-tolerated regimen but achieved the highest rates of right colonic cleansing and the lowest rate of incomplete colonoscopies. There were no statistical differences in the rates of rectosigmoid and mid-gut cleansing among the three agents. SS was by far the preferred purgative in the taste assessment study. Addition of flavour increased significantly taste scores for PEG-EOS., Conclusion: For adequate bowel cleansing PEG-EOS is the most effective but is the least tolerated and least preferred among patients. Addition of flavour increases significantly patients' acceptance of PEG-EOS.

This feature article describes the development of synthetic zinc(ii)-dipicolylamine (ZnDPA) receptors as selective targeting agents for anionic membranes in cell culture and living subjects. There is a strong connection between anionic cell surface charge and disease, and ZnDPA probes have been employed extensively for molecular imaging and targeted therapeutics. Fluorescence and nuclear imaging applications include detection of diseases such as cancer, neurodegeneration, arthritis, and microbial infection, and also quantification of cell death caused by therapy. Therapeutic applications include selective targeting of cytotoxic agents and drug delivery systems, photodynamic inactivation, and modulation of the immune system. The article concludes with a summary of expected future directions.

Background and Aims: Previous studies comparing sodium picosulfate/magnesium citrate (SPMC) with polyethylene glycol (PEG) drew inconsistent conclusions. We conducted a meta-analysis to compare the performance of the two agents for colonoscopy preparation., Methods: A search of randomized controlled trials (RCTs) up to July 2015 was acquired, using MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. We calculated the pooled estimates of bowel cleanliness, polyp/adenoma detection rate (PDR/ADR), completion of preparation, willingness to repeat identical bowel preparation, and adverse events by using relative risk (RR) with random-effects models. A non-inferiority analysis was performed, comparing SPMC to PEG for bowel cleaning efficacy., Results: A total of 25 RCTs were qualified for analysis. There was no statistically significant difference between the two agents in bowel cleanliness, but the effect direction showed a trend in favor of PEG (RR 0.93; 95 % CI 0.86-1.01, P = 0.07). The non-inferiority analysis demonstrated the non-inferiority of SPMC by retaining at least 90 % of the effect of PEG. Similarly, there was no significant difference between the two agents in PDR (RR 0.94; 95 % CI 0.82-1.08, P = 0.37) and ADR (RR 0.88; 95 % CI 0.74-1.05, P = 0.16). However, a higher proportion of patients were likely to complete SPMC preparation (RR 1.08; 95 % CI 1.04-1.13, P < 0.001) and were willing to repeat SPMC preparation (RR 1.44; 95 % CI 1.25-1.67, P < 0.001). The total number of adverse events was significantly lower in the SPMC group (RR 0.78; 95 % CI 0.66-0.93, P = 0.004)., Conclusions: SPMC, with better tolerability and less frequent adverse events, demonstrated non-inferior bowel cleaning efficacy than that of the PEG. Large-scale, well-organized, head-to-head studies are warranted.

Cutaneous leishmaniasis is a neglected tropical disease that causes painful lesions and severe disfigurement. Modern treatment relies on a few chemotherapeutics with serious limitations, and there is a need for more effective alternatives. This study describes the selective targeting of zinc(II)-dipicolylamine (ZnDPA) coordination complexes toward Leishmania major, one of the species responsible for cutaneous leishmaniasis. Fluorescence microscopy of L. major promastigotes treated with a fluorescently labeled ZnDPA probe indicated rapid accumulation of the probe within the axenic promastigote cytosol. The antileishmanial activities of eight ZnDPA complexes were measured using an in vitro assay. All tested complexes exhibited selective toxicity against L. major axenic promastigotes, with 50% effective concentration values in the range of 12.7 to 0.3 μM. Similar toxicity was observed against intracellular amastigotes, but there was almost no effect on the viability of mammalian cells, including mouse peritoneal macrophages. In vivo treatment efficacy studies used fluorescence imaging to noninvasively monitor changes in the red fluorescence produced by an infection of mCherry-L. major in a mouse model. A ZnDPA treatment regimen reduced the parasite burden nearly as well as the reference care agent, potassium antimony(III) tartrate, and with less necrosis in the local host tissue. The results demonstrate that ZnDPA coordination complexes are a promising new class of antileishmanial agents with potential for clinical translation., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Objective: This study was aimed to evaluate the efficacy and safety of two low-volume agents, polyethylene glycol (PEG)-3350 plus ascorbic acid (PEG + Asc) and sodium picosulfate with magnesium citrate (SPMC), for bowel preparation., Methods: We performed a prospective, endoscopist-blinded, single-center, randomized controlled trial comparing PEG + Asc with SPMC to evaluate the bowel cleansing efficacy of the two regimens using the modified Ottawa bowel preparation scale (OBPS) and the Aronchick scale. Patients' taste and overall tolerance were assessed with a questionnaire., Results: In total, 200 patients were randomized to receive either PEG + Asc (n = 98) or SPMC (n = 102). Both treatments were similarly efficacious in bowel cleansing, based on the modified OBSP (PEG + Asc 4.01 ± 2.29 vs SPMC 3.86 ± 2.47, P = 0.62) and Aronchick scale (PEG + Asc 1.96 ± 0.70 vs SPMC 1.89 ± 0.70, P = 0.42). Patient-reported taste and tolerance of each regimen, as reported by the questionnaire, were significantly greater in the PEG + Asc group than in the SPMC group (P = 0.01). In terms of adverse events, dizziness was more frequently observed in the PEG + Asc group (P = 0.03), whereas nausea was more common in the SPMC group (P = 0.02)., Conclusions: PEG + Asc and SPMC show similar efficacy for bowel preparation. However, patient's overall tolerance is higher in the PEG + Asc group., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: The purpose of this randomised study was to compare the quality of bowel cleansing using either polyethylene glycol (PEG) or sodium picosulphate (NaPico) (primary outcome) in relation to the tolerability and acceptance of these laxatives among children and their caregivers (secondary outcome)., Methods: The study was a randomised controlled trial that was conducted as an investigator-blinded study within the Department of Paediatrics of Skåne University Hospital in Malmö, Sweden. A total of 72 children (10-18 years of age) were randomly placed into 1 of 2 groups (PEG or NaPico). The Ottawa Bowel Preparation Quality Score was used to evaluate the quality of bowel cleansing. A total of 2 different questionnaires were used to evaluate both the acceptability and tolerability of the laxatives., Results: In total, 71 children completed the bowel cleansing. Of these 71 cleanses, 67 protocols were analysed according to the Ottawa Bowel Preparation Quality Score. No significant difference in bowel cleansing quality was detected between the 2 groups. Rates of acceptability and tolerability were significantly higher in the NaPico group than in the PEG group., Conclusions: In the present study, both laxatives were found to be satisfactory in terms of aiding the performance of an uncomplicated and successful colonoscopy. NaPico was, however, more tolerable to the children than PEG, and both, the children and their caregivers, were more accepting of NaPico than of PEG. Consequently, NaPico can be recommended as the option for bowel cleansing in children ages 10 years and older.

The impact of the treatment method proposed, using antioxidant therapy in patients, suffering the burns, on the speed and efficacy of the donor's wounds healing in their extremities was studied. In a control group of patients a standard treatment of the donor's wounds in extremities was conducted, while in the main group of patients the treatment was added with lymphotropic injection of antioxidant preparation Mexidol. Due to application of the method proposed, the wounds healing in the main group of the injured persons have had occurred significantly faster, than in the patients of a control group, and the complications of the wounds healing were absent.

Aim: To evaluate the activity of neuron specific enolase (NSE) in patients with primary hypothyroidism (PGT) treated with mexidol., Material and Methods: Patients with PGT (n=110) were examined before and after treatment. Neuropsychological and neurological status of the patients was studied. To assess the status of the peripheral nervous system, electroneuromyography was performed and serum NSE level was determined., Results and Conclusion: The NSE activity depended on gender, age of the patient, duration of endocrinopathy and presence/absence of neurological symptoms. The clear positive dynamics of the majority of the parameters studied was noted during mexidol treatment. The efficacy of antioxidant therapy in these patients was confirmed.

Objective: To determine the antihypoxic efficacy of mexidol in carotid endarterectomy (CE) procedure in patients with cerebral atherosclerotic stenosis using cerebral oximetry., Material and Methods: Clinical/psycho/neurological monitoring was performed in 109 patients with internal carotid artery stenosis of 69±7.0% and neurological symptoms of cerebral ischemia, 2-3 degree, in pre- and postoperative periods. Cerebral oximetry was carried out perioperatively. Fifty-four patients were treated with mexidol in a dose of 1000 mg/day for 14-15 days and 55 patients did not received mexidol., Results and Conclusion: The difference in initial brain oxygenation (rSO2) between the main and comparison groups was shown (60.8±5.0 and 47.29±5.5%, respectively). During operation, the degree of blood oxygenation in these groups decreased by 57% and 41%, respectively. On day 7, sinificant differences in the Schulte test in two groups of patients with similar neurological status were found considering efficiency of work and mental stability before and after operation. No differences were found in the comparison group. Mexidol used for antihypoxic brain protection in carotid endarterectomy of patients with cerebral atherosclerotic stenosis significantly reduces the degree of cerebral hypoxia, decreases the duration of surgery, improves neurological status of patients and performance of psychological tests in postoperative period.

Objectives: Evaluation of effectiveness of Mexidol in optimization of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients., Material and Methods: Authors analyzed the indicators of lipid status: total cholesterol, low-density lipoproteins, high density lipoproteins, triglycerides and concentration of platelet factor-4, β-tromboglobulin, von Willebrand factor in 68 patients with acute ischemic stroke and diabetes mellitus. Authors investigate the dynamics of these parameters (1(st), 21(st), 3-d and 6(th) month after onset stroke) depending on timing and dose of Mexidol., Results: Long time therapy of Mexidol may optimize of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients.